To explain the role of blood in hemostasis and vascular function, certain aspects of coagulation, fibrinolysis and complement will be examined. Vascular function can be altered by certain polypeptides, and a polypeptide-kinin extractable from hereditary angioneurotic edema (HANE) plasma can increase vascular permeability. Definition of the chemical nature of this polypeptide should allow analysis of its mechanism of action, and understanding of its function in normal individuals may be gained through studies with antibody to this peptide. Serum inhibitor of Cl esterase (Cl-INH) can block plasma enzymes which act in coagulation, fibrinolysis and kinin release as well as activated first component of complement (Cl). Non-functional allotypes of the inhibitor in certain persons with HANE may block some of these enzymes, but not Cl. Characterization of the capacity of certain of these allotype inhibitor proteins should advance understanding of the mechanism of inhibitory effects of Cl-INH. In determining mechanisms of indirect activation of the first component of complement in HANE plasma by activated Hageman factor, added insights into relationships between clotting and complement action should be gained. Plasmin may be involved, and variability of its hydrolytic actions will be evaluated by examining some products of proteolysis by plasmin preparations.